This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The catalytic machinery for the bacterial phosphotriesterase (PTE) is capable of detoxifying organophosphates. Organophosphates such as tabun, sarin, soman, cyclosarin, and VX are among the most toxic and deadly nerve agents ever reported. Since these compounds are easy to synthesize and distribute they can be used as weapons. The active site of PTE will be re-engineered through rational and combinatorial mutagenesis to create a library of mutant enzyme with altered catalytic properties aimed at degrading organophosphates. Collaborators will test and optimize enzymes for their ability to act upon these nerve agents. Our objectives will be to determine high-resolution crystal structures to correlate structural details with the catalytic properties of the mutant enzymes.